Effect of Low Protein Diet on Low Dose Chronic Aflatoxin B1Induced Hepatic Injury in Rhesus Monkeys

Abstract

The role of dietary protein in low dose chronic alfatoxin B1 (AFB1) liver injury in Rhesus monkeys has been studied using 0.16 and 0.5 ppm of AFB1 in diet. The high and low protein diet contained 20% and 5% casein, respectively. Following 32 weeks of intoxication with 0.16 ppm of AFB1, histological examination revealed mild alterations in low protein group only. However, distinct histochemical and ultra-structural alterations indicative of toxic liver injury are present in both the groups fed AFB1, though more prominent in animals fed a low protein diet. Monkeys on low protein diet surviving for 90 weeks or more show foci of preneoplastic lesions, whereas those on high protein diet reveal no such alterations at the corresponding time interval. With 0.5 ppm of AFB1 in diet, the pattern of toxic liver injury is similar to that of 0.16 ppm of AFB1 in diet. However, the liver damage is more prominent with this dose. The hepatic injury again is more accentuated in the low protein group as compared with the high protein group. No preneoplastic lesions are observed, possibly due to a poor survival (less than 70 weeks) in the low protein animals with this dose. The animals in the high protein group surviving even beyond 90 weeks do not show any preneoplastic/neoplastic lesions. It appears that in the simian model used by us, the liver injury caused by AFB1 is accentuated by simultaneous restriction of dietary protein and in animals on such combined regimen preneoplastic lesions appear around 90 weeks of experiment. These observations suggest a synergism between protein calorie malnutrition and aflatoxin induced hepatocarcinogenesis and may explain the higher incidence of hepatocellular carcinoma in certain areas of the world where contamination of foods with aflatoxin and malnutrition are prevalent.